NICE Makes Pembrolizumab Available in Frontline NSCLC Through Cancer Drugs Fund

The UK’s National Institute for Health and Care Excellence (NICE) will allow first-line use of pembrolizumab (Keytruda) for non—small cell lung cancer (NSCLC) as part of the Cancer Drugs Fund (CDF).

The fund allows patients access to therapies that are still under investigation for efficacy or cost-effectiveness. A treatment is eligible for CDF funding “when NICE considers there to be plausible potential for the drug/indication to satisfy the criteria for routine commissioning, but where there is significant remaining clinical uncertainty.”

To be eligible for treatment, patients must also have no EGFR or ALK mutations. Furthermore, only patients whose tumors show 50% or more PD-L1 expression will be eligible. The National Health Service (NHS) began testing for the mutation in April.

NICE denied Merck’s request to allow routine first-line use of the PD-1 inhibitor in newly diagnosed patients, citing its high cost and outstanding questions about overall survival (OS) benefits.

NICE previously rejected pembrolizumab in first-line for this patient population in draft guidance published in March. The drug is already approved for second-line use in patients with refractory disease.

The company has agreed to provide pembrolizumab to the NHS at a discount for a limited time. Merck must prove the drug’s value, either through further clinical trials or real-world data, and NHS will fully reimburse Merck or the company will lose all funding after that limited period expires.

Finding new ways to treat NCLSC is of crucial importance in the UK, which saw lung cancer prevalence increase 10% from 2008 to 2012. The charitable organization McMillan Cancer Support estimates that as many as 2.5 million people living with lung cancer in the UK and predicts that number will rise to 4 million by 2030. The NHS says lung cancer is the leading cause of cancer-related deaths, and results from the EUROCARE population study showed that the UK and Ireland had the poorest 5-year survival rate for lung cancer in Europe.

In the United States, the FDA approved pembrolizumab for first-line treatment of patients with metastatic NSCLC whose tumors have ≥50% PD-L1 expression in December 2016 based on phase III results from the KEYNOTE-024 trial.^1,2 Longer-term data from KEYNOTE-024 trial is due in February 2018, and more robust survival data could help the drug gain full approval in the UK.

In KEYNOTE-024, the estimated 6-month OS rate was 80.2% with pembrolizumab versus 72.4% with chemotherapy (HR, 0.60; 95% CI, 0.41-0.89; P = .005). Median progression-free survival (PFS) was 10.3 months with pembrolizumab versus 6.0 months with chemotherapy (HR, 0.50; 95% CI, 0.37-0.68; P <.001).

The 6-month PFS rate was 62.1% in the pembrolizumab arm versus 50.3% with chemotherapy. This benefit remained consistent across subgroups. At the time of the analysis, median OS had not yet been reached. The objective response rate with pembrolizumab was 44.8% compared with 27.8% with chemotherapy. The duration of response was not reached in the immunotherapy arm versus 6.3 months with chemotherapy.

The benefits of pembrolizumab were not as strong when compared with chemotherapy regimens containing pemetrexed (HR, 0.63; 95% CI, 0.44-0.91). There was a 71% reduction in the risk for progression or death with pembrolizumab When pemetrexed was omitted (HR, 0.29; 95% CI, 0.17-0.50).

Researchers observed fewer treatment-related adverse events (AEs) in patients assigned to pembrolizumab compared with chemotherapy (73.4% vs 90%). Grade ≥3 AEs were significantly more common with chemotherapy (53.3%) compared with pembrolizumab (26.6%).

Serious AEs were similar for pembrolizumab (21.4%) and chemotherapy (20.7%). AEs led to treatment discontinuation for 7.1% of patients in the pembrolizumab arm versus 10.7% of those receiving chemotherapy.

The most common treatment-related AEs of any severity for pembrolizumab were diarrhea (14.3%), fatigue (10.4%), and pyrexia (10.4%). With chemotherapy, the most common AEs of any-grade were anemia (44%), nausea (43.3%), and fatigue (28.7%). Immune-mediated AEs occurred in 29.2% of those treated with pembrolizumab versus 4.7% of those in the chemotherapy arm.

Earlier this months, the FDA granted accelerated approval to pembrolizumab in combination with pemetrexed plus carboplatin as a frontline treatment for patients with metastatic or advanced nonsquamous NSCLC.

References

1. Reck M, Rodgriguez-Abreu D, Robinson AG, et al. KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA8.
2. Reck M, Rodgriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1—Positive Non–Small-Cell Lung Cancer [published online October 9, 2016]. N Engl J Med. DOI: 10.1056/NEJMoa1606774.